Update on Remestemcel-L For the Treatment of COVID-19 ARDS and Steroid-Refractory Acute GVHDQuarterly Activity Report

NEW YORK, Oct. 29, 2020 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today provided an update on the potential pathway to marketing approval for its lead product candidate remestemcel-L. It also provided a financial report for the first quarter ended September 30, 2020.

Mesoblast Chief Executive Dr Silviu Itescu stated: “We believe the immunomodulatory properties of remestemcel-L position this potential therapy at the forefront of treatment for severe and life-threatening inflammatory conditions, including COVID-19 acute respiratory distress syndrome (ARDS) and steroid-refractory acute graft versus host disease (SR-aGVHD). We are pursuing an accelerated approval pathway for remestemcel-L in the treatment of children with SR-aGVHD, and a parallel approval pathway for COVID-19 ARDS if the randomized controlled Phase 3 trial is positive.”

Children with Steroid-Refractory Acute Graft Versus Host Disease
In August, the Oncologic Drugs Advisory Committee (ODAC)¹ of the United States Food and Drug Administration (FDA) voted 9:1 that the available data from a single-arm Phase 3 trial and evidence from additional studies support the efficacy of remestemcel-L in pediatric patients with SR-aGVHD. Despite the overwhelming ODAC vote, in September the FDA recommended that Mesoblast conduct at least one additional randomized, controlled study in adults and/or children to provide further evidence of the effectiveness of remestemcel-L for SR-aGVHD.

Mesoblast believes that remestemcel-L meets the criteria for accelerated approval as there are currently no approved treatments for this life-threatening condition in children under 12. Mesoblast has formally requested a Type A meeting with the FDA to discuss a potential accelerated approval of the Biologics License Application (BLA) for remestemcel-L for the treatment of SR-aGVHD in children, with an additional randomized controlled study in patients 12 years and older as a post-approval requirement. Mesoblast expects this meeting will occur in November.

Adults with COVID-19 ARDS
As cases of COVID-19 surge in the United States and globally, deaths continue to increase from ARDS in ventilator-dependent patients as a result of an overactive immune response in the lungs to COVID-19. It is now evident that in both adults and children COVID-19 causes severe inflammation of other organ systems in addition to the lungs, including the heart, brain and kidneys. The immunomodulatory mechanism of action of remestemcel-L may be beneficial in the treatment of ARDS as well as in involvement of other organ systems.

Indeed, nine of 12 ventilator-dependent adult patients with COVID-19 ARDS who received two doses of remestemcel-L under emergency compassionate use at New York’s Mt Sinai Hospital were successfully discharged within a median of 10 days. Additionally, two COVID-19 infected children with multisystem inflammatory syndrome (MIS-C) who received remestemcel-L for severe heart failure fully recovered heart function and were discharged within 30 hours of the second dose.

To confirm these pilot data, remestemcel-L is being evaluated for its potential to reduce mortality in a Phase 3 randomized controlled trial of up to 300 ventilator-dependent adults with moderate or severe COVID-19 ARDS. The dosing regimen in the Phase 3 is the same as in the pilot trial. Trial enrollment across more than 20 hospitals in the United States has surpassed 50% of the total 300 patient target. The trial’s first 135 patients will complete 30 days of follow up during October, after which the independent Data Safety Monitoring Board (DSMB) will perform an interim analysis of the trial’s primary endpoint of all-cause mortality within 30 days of randomization. The DSMB is expected to inform Mesoblast in early November on whether the trial should proceed as planned, or should stop early. A further interim analysis is planned after 60% of the trial has been enrolled.

Crohn’s Disease
According to recent estimates, more than three million people (1.3%) in the United States alone have inflammatory bowel disease, with more than 33,000 new cases of Crohn’s disease and 38,000 new cases of ulcerative colitis diagnosed every year.^2-4 Despite recent advances, approximately 30% of patients are primarily unresponsive to anti-TNFα agents and even among responders, up to 10% will lose their response to the drug every year. Up to 80% of patients with medically-refractory Crohn’s disease eventually require surgical treatment of their disease,⁵ which can have a devastating impact on quality of life.

A randomized, controlled study of remestemcel-L delivered by an endoscope directly to the areas of inflammation and tissue injury in up to 48 patients with medically refractory Crohn’s disease and ulcerative colitis has commenced at Cleveland Clinic. Mesoblast’s objective is to confirm the potential for remestemcel-L to induce luminal healing and early remission in a wider spectrum of diseases with severe inflammation of the gut, in addition to SR-aGVHD. The investigator-initiated study at Cleveland Clinic is the first in humans using local cell delivery in the gut, and will enable Mesoblast to compare clinical outcomes using this delivery method with results from an ongoing randomized, placebo-controlled trial in patients with biologic-refractory Crohn’s disease where remestemcel-L was administered intravenously.

Chronic Heart Failure
In the United States alone, of more than 6.5 million patients with chronic heart failure, there are more than 1.3 million patients with advanced stage of the disease.⁶ The objective of treatment with Mesoblast’s allogeneic cellular product candidate REVASCOR^® is to reduce or reverse the severe inflammatory process in the damaged heart of these patients, and thereby prevent or delay further progression of heart failure or death. In an earlier randomized placebo-controlled 60-patient Phase 2 trial, a single intra-myocardial injection of REVASCOR at the dose administered in the subsequent Phase 3 trial prevented any hospitalizations or deaths over three years of follow-up in patients with advanced chronic heart failure. Results from Mesoblast’s randomized placebo-controlled Phase 3 trial in patients with advanced forms of New York Heart Association Class II or Class III disease are expected during Q4 CY2020.

Chronic Low Back Pain
There is a significant need for a safe, efficacious and durable treatment in patients with chronic low back pain due to severely inflamed degenerative disc disease, affecting over 3.2 million patients in the United States and approximately 4 million in the EU5.⁷ Results from a Phase 3 randomized placebo-controlled trial evaluating Mesoblast’s product candidate in patients with chronic low back pain due to degenerative disc disease are expected during Q4 CY2020. In parallel, Mesoblast and its partner Grünenthal GmbH are collaborating on the clinical protocol for a confirmatory Phase 3 trial in Europe.

Cash Flow Report for the First Quarter FY2021
Cash on hand at the end of the quarter was US$108.1 million. Over the next 12 months, Mesoblast may have access to an additional US$67.5 million through existing financing facilities and strategic partnerships.

Total Operating Activities excluding product inventory resulted in net cash usage of US$23.0 million in the quarter ended September 30, 2020. In addition, $5.2 million was invested in RYONCIL^® (remestemcel-L) commercial inventory in anticipation of product launch for either children with SR-aGVHD or COVID-19 patients with moderate to severe ARDS.

• Research and Development payments were US$9.9 million for the current quarter compared to US$7.8 million for quarter ended September 30, 2019. The increase was primarily due to recruitment activities for our Phase 3 trial of remestemcel-L in COVID-19 patients with moderate to severe ARDS.
• Product manufacturing and operating costs were US$5.2 million for the current quarter compared to US$3.5 million for quarter ended September 30, 2019. The increase was primarily due to investment in scale-up and increased capacity requirements of remestemcel-L in parallel to development for COVID-19 ARDS.
• Royalty receipts received from JCR Pharmaceuticals Co. Ltd for the sales of TEMCELL HS Inj.^(R)8 in Japan for the treatment of aGVHD were US$0.7 million for the current quarter compared to US$1.7 million for the quarter ended September 30, 2019. The decrease was due to a temporary shutdown in production as JCR expands its facility capacity to meet increasing demand far in excess of its initial forecast (as announced by JCR Pharmaceuticals on July 31, 2020).
• Payments to Related Parties, detailed in Item 6 of the Appendix 4C cash flow report for the quarter, comprise approximately US$387,000 in Non-executive Director fees and Executive Director’s salary.

About Mesoblast
Mesoblast Limited (Nasdaq:MESO; ASX:MSB) is a world leader in developing allogeneic (off-the-shelf) cellular medicines. The Company has leveraged its proprietary mesenchymal lineage cell therapy technology platform to establish a broad portfolio of commercial products and late-stage product candidates. Mesoblast has a strong and extensive global intellectual property (IP) portfolio with protection extending through to at least 2040 in all major markets. The Company’s proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide.

Remestemcel-L is being developed for inflammatory diseases in children and adults including steroid-refractory acute graft versus host disease and moderate to severe acute respiratory distress syndrome. Mesoblast is completing Phase 3 trials for its product candidates for advanced heart failure and chronic low back pain. Two products have been commercialized in Japan and Europe by Mesoblast’s licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets.

Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @Mesoblast

1.This vote includes a change to the original vote by one of the ODAC panel members after electronic voting closed.
2.CDC Facts and Figures 2015.
3.Globaldata Pharmapoint 2018.
4.Dahlhamer JM, MMWR Morb Mortal Wkly Rep. 2016;65(42):1166–1169.
5.Crohn’s and Colitis Foundation
6.AHA’s 2017 Heart Disease and Stroke Statistics
7.Decision Resources: Chronic Pain December 2015
8.TEMCELL^® HS Inj. is a registered trademark of JCR Pharmaceuticals Co. Ltd.

Forward-Looking Statements
This announcement includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. Forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of Mesoblast’s preclinical and clinical studies, and Mesoblast’s research and development programs; Mesoblast’s ability to advance product candidates into, enroll and successfully complete, clinical studies, including multi-national clinical trials; Mesoblast’s ability to advance its manufacturing capabilities; the timing or likelihood of regulatory filings and approvals, manufacturing activities and product marketing activities, if any; the commercialization of Mesoblast’s product candidates, if approved; regulatory or public perceptions and market acceptance surrounding the use of stem-cell based therapies; the potential for Mesoblast’s product candidates, if any are approved, to be withdrawn from the market due to patient adverse events or deaths; the potential benefits of strategic collaboration agreements and Mesoblast’s ability to enter into and maintain established strategic collaborations; Mesoblast’s ability to establish and maintain intellectual property on its product candidates and Mesoblast’s ability to successfully defend these in cases of alleged infringement; the scope of protection Mesoblast is able to establish and maintain for intellectual property rights covering its product candidates and technology; estimates of Mesoblast’s expenses, future revenues, capital requirements and its needs for additional financing; Mesoblast’s financial performance; developments relating to Mesoblast’s competitors and industry; and the pricing and reimbursement of Mesoblast’s product candidates, if approved. You should read this press release together with our risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblast’s actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise.

Release authorized by the Chief Executive.

For further information, please contact: